Protein / target

Gamma-aminobutyric acid receptor subunit delta

Encoded byGABRDO14764Homo sapiensSwiss-Prot

UniProt: O14764 Ensembl: ENSG00000187730 HGNC: HGNC:4084 NCBI Gene: 2563

Clinically validated

Therapeutic maturity

Approved medicines

Open Targets target-level

View by indication →

Clinical trials

Small-molecule tractable

Druggability

Approved Drug

Protein at a glance

Biological role

Chloride channel

Strongest disease association

Generalized epilepsy with febrile seizures-plus

Via encoding gene GABRD · Genetic literature evidence · score 0.86

Therapeutic position

Established drug target

Small molecules

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

Delta subunit of the heteropentameric ligand-gated chloride channel gated by gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the brain.

View complete UniProt function annotation

Delta subunit of the heteropentameric ligand-gated chloride channel gated by gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the brain (PubMed:35355020). GABA-gated chloride channels, also named GABA(A) receptors (GABAAR), consist of five subunits arranged around a central pore and contain GABA active binding site(s) located at the alpha and beta subunit interface(s) (PubMed:35355020). When activated by GABA, GABAARs selectively allow the flow of chloride anions across the cell membrane down their electrochemical gradient (PubMed:35355020). GABAARs containing delta/GABRD subunits are predominantly located in extrasynaptic or perisynaptic positions on hippocampus and cerebellar granule cells, and contribute to the tonic GABAergic inhibition (By similarity). GABAAR containing alpha-4-beta-3-delta subunits can simultaneously bind GABA and histamine where histamine binds at the interface of two neighboring beta subunits, which may be involved in the regulation of sleep and wakefulness (PubMed:35355020)

Subcellular location

Cell membrane

Domains and Gene Ontology detail (17)

Gene Ontology

Caxon
Cchloride channel complex
Cdendrite
CGABA-A receptor complex
CGABA-ergic synapse
Cglutamatergic synapse
Cneuronal cell body
Cplasma membrane
Cpostsynaptic membrane
Fchloride channel activity
FGABA-A receptor activity
Ftransmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential

452 aa · 51 kDa

Biological roles

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Inhibitory neurotransmissionUniProt · GOChloride transportUniProt · GOLigand-gated signallingUniProt · GOIon channel gatingGO

View supporting evidence

Inhibitory neurotransmission

·Delta subunit of the heteropentameric ligand-gated chloride channel gated by gamma-amino…
·GABA-ergic synapse
·synaptic transmission, GABAergic

Chloride transport

·Delta subunit of the heteropentameric ligand-gated chloride channel gated by gamma-amino…
·chloride channel complex
·chloride channel activity

Ligand-gated signalling

·Delta subunit of the heteropentameric ligand-gated chloride channel gated by gamma-amino…
·transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic…

Ion channel gating

·transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic…

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Interaction neighbourhood

STRING v12.0

Proteins with the strongest functional or physical association. Node size and line weight reflect STRING confidence; hover or select a partner to inspect one association.

10 strongest partners — larger node and heavier line mean higher confidence

Functional and physical associations from STRING v12.0. Only associations with this protein are drawn — partner-to-partner links are not part of this evidence.

Approved medicines with mapped indications

9 medicines · 6 areas

Approved therapies targeting this protein, grouped by what they are approved to treat — the disease-first view of the medicines below. Relationships come from the canonical approved-indication graph (ChEMBL phase-4), the same source as the drug cards.

Epilepsy5 medicines

cenobamate clonazepam ganaxolone Midazolam topiramate

Seizures5 medicines

cenobamate clobazam clonazepam ganaxolone topiramate

Anxiety Disorders3 medicines

alprazolam lorazepam meprobamate

Status Epilepticus2 medicines

lorazepam Midazolam

Epileptic Syndromes1 medicine

ganaxolone

Migraine Disorders1 medicine

topiramate

58 medicines meet Open Targets' target-level approved-medicine definition; the 9 shown here are those on this page with a canonical approved disease indication in the graph. Approved indications from ChEMBL (phase-4), via the canonical drug→disease graph.

Drugs targeting this protein

How approved and investigational drugs engage this protein — mechanism and action type, direct vs complex targeting, and how broadly each acts across other targets. A drug-first view (the section above groups the approved ones disease-first); direct binders with few recorded targets are listed first.

Midazolam

ApprovedPositive allosteric modulator

GABA-A receptor; anion channel positive allosteric modulator

Indicated for Epilepsy, Status Epilepticus

Acts on a complex — shared with GABRG2, GABRB3, GABRG3 +12 more · 1 of 16 recorded protein targets — broad pharmacology

Isoflurane

ApprovedPositive allosteric modulator

GABA-A receptor; anion channel positive allosteric modulator

Acts on a complex — shared with GABRG2, GABRB3, GABRG3 +12 more · 1 of 23 recorded protein targets — broad pharmacology

Halothane

ApprovedPositive allosteric modulator

GABA-A receptor; anion channel positive allosteric modulator

Acts on a complex — shared with GABRG2, GABRB3, GABRG3 +12 more · 1 of 23 recorded protein targets — broad pharmacology

sevoflurane

ApprovedPositive allosteric modulator

GABA-A receptor; anion channel positive allosteric modulator

Acts on a complex — shared with GABRG2, GABRB3, GABRG3 +12 more · 1 of 23 recorded protein targets — broad pharmacology

propofol

ApprovedPositive allosteric modulator

GABA-A receptor; anion channel positive allosteric modulator

Acts on a complex — shared with GABRG2, GABRB3, GABRG3 +12 more · 1 of 16 recorded protein targets — broad pharmacology

clobazam

ApprovedPositive allosteric modulator

GABA-A receptor; anion channel positive allosteric modulator

Indicated for Seizures

Acts on a complex — shared with GABRG2, GABRB3, GABRG3 +12 more · 1 of 16 recorded protein targets — broad pharmacology

View all 13 targeting drugs

clonazepam

ApprovedPositive allosteric modulator

GABA-A receptor; anion channel positive allosteric modulator

Indicated for Epilepsy, Seizures

Acts on a complex — shared with GABRG2, GABRB3, GABRG3 +12 more · 1 of 16 recorded protein targets — broad pharmacology

lorazepam

ApprovedPositive allosteric modulator

GABA-A receptor; anion channel positive allosteric modulator

Indicated for Anxiety Disorders, Status Epilepticus

Acts on a complex — shared with GABRG2, GABRB3, GABRG3 +12 more · 1 of 16 recorded protein targets — broad pharmacology

meprobamate

ApprovedAgonist

GABA-A receptor; anion channel agonist

Indicated for Anxiety Disorders

Acts on a complex — shared with GABRG2, GABRB3, GABRG3 +12 more · 1 of 16 recorded protein targets — broad pharmacology

topiramate

ApprovedPositive modulator

GABA-A receptor; anion channel positive modulator

Indicated for Epilepsy, Migraine Disorders, Seizures

Acts on a complex — shared with GABRG2, GABRB3, GABRG3 +12 more · 1 of 37 recorded protein targets — broad pharmacology

cenobamate

ApprovedPositive allosteric modulator

GABA-A receptor; anion channel positive allosteric modulator

Indicated for Epilepsy, Seizures

Acts on a complex — shared with GABRG2, GABRB3, GABRG3 +12 more · 1 of 26 recorded protein targets — broad pharmacology

ganaxolone

ApprovedPositive allosteric modulator

GABA-A receptor; anion channel positive allosteric modulator

Indicated for Epilepsy, Epileptic Syndromes, Seizures

Acts on a complex — shared with GABRG2, GABRB3, GABRG3 +12 more · 1 of 16 recorded protein targets — broad pharmacology

alprazolam

ApprovedPositive allosteric modulator

GABA-A receptor; anion channel positive allosteric modulator

Indicated for Anxiety Disorders

Acts on a complex — shared with GABRG2, GABRB3, GABRG3 +12 more · 1 of 16 recorded protein targets — broad pharmacology

ChEMBL mechanism, action type, target identity and approved indications. Open Targets clinical status.

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene GABRD

Gene-level evidence surfaced through the gene GABRDthat encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Generalized epilepsy with febrile seizures-plus

0.81Well supported

Genetic evidence dominant · Open Targets 0.74

Epilepsy

0.76Well supported

Clinical evidence dominant · Open Targets 0.61

Major depressive disorder

0.75Moderately supported

Clinical evidence dominant · Open Targets 0.61

Anxiety Disorders

0.75Moderately supported

Clinical evidence dominant · Open Targets 0.60

Alcoholism

0.73Moderately supported

Clinical evidence dominant · Open Targets 0.59

View evidence synthesis (5)

Generalized epilepsy with febrile seizures-plusWell supported

0.81

agreement 0.69–0.93

Genetic82%Animal model18%Genetic literaturedup

Open Targets aggregate 0.74 · 2 independent evidence families · 1 not counted as duplicate

EpilepsyWell supported

0.76

agreement 0.64–0.87

Clinical96%Literature4%Genetic literature1%

Open Targets aggregate 0.61 · 3 independent evidence families

Major depressive disorderModerately supported

0.75

agreement 0.59–0.90

Clinical99%Literature2%

Open Targets aggregate 0.61 · 2 independent evidence families

Anxiety DisordersModerately supported

0.75

agreement 0.59–0.90

Clinical99%Literature1%

Open Targets aggregate 0.60 · 2 independent evidence families

AlcoholismModerately supported

0.73

agreement 0.57–0.89

Clinical100%Literature0%

Open Targets aggregate 0.59 · 2 independent evidence families

The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.

Show all associations

Generalized epilepsy with febrile seizures-plus0.74

Epilepsy0.61

Major depressive disorder0.61

Anxiety Disorders0.60

Alcoholism0.59

Drug development

72 compounds recorded · 58 approved · 9 in clinical development · 5 earlier-stage

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 13 drugs that target this protein in Forefront's canonical graph (9 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (10)

ESZOPICLONEApproval

FLUMAZENILApproval

SECOBARBITAL SODIUMUnknown

PAGOCLONEPhase 2 3

THIOPENTAL SODIUMPhase 1

METHAQUALONE HYDROCHLORIDEUnknown

REMIMAZOLAM BESYLATEApproval

RESEQUINILPhase 2

ETOMIDATEApproval

HALOTHANEApproval

Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.

Tractability

Small molecules — Strong

Approved Drug and Structure with Ligand support this modality.

Antibodies — Emerging

Feasibility evidence (go cc high conf and uniprot loc med conf) — no clinical-stage drug of this modality recorded.

Protein degraders — Emerging

Feasibility evidence (database ubiquitination and small molecule binder) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (9)

SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · Druggable FamilyAB · GO CC high confAB · UniProt loc med confAB · UniProt SigP or TMHMMPR · Database UbiquitinationPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Clinical trials

Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein. Ranked by active status, then clinical phase and recency, and spread across the targeting drugs.

Comparison of Hemodynamics and Respiratory Function Between Ciprofol and Propofol in Elderly Patients Undergoing Non-intubated General AnesthesiaPHASE4

NOT_YET_RECRUITING · via propofol · NCT07670923

Intravenous Acetaminophen and Ketorolac for Pain Management During Extracorporeal Shockwave Lithotripsy: A Quasi-Randomized Controlled TrialPHASE4

ENROLLING_BY_INVITATION · via Midazolam · NCT07368738

Management of Acute Tinnitus With Migraine Medications: A Randomized Clinical TrialPHASE4

ACTIVE_NOT_RECRUITING · via topiramate · NCT06799169

Effect of Volatile-based Versus Total Intravenous Anesthesia on Cerebral Homeostasis and Neucognitive Function in Patients Undergoing Elective Craniotomy for Brain Tumor Excision.PHASE4

RECRUITING · via sevoflurane · NCT06779890

View all trials (26)

Pain, Anxiety and Anesthetic Satisfaction for Patient With Different State Anxiety Underwent Cataract Surgery With Topical Anesthesia. An Extension Test of Whether to Use Oral Anti-anxiety Drugs (Alprazolam) When Patients Choose Second Eye Cataract Surgery After Unblinding, and Analyze Their Anxiety, Satisfaction and Pain Satisfaction.PHASE4

RECRUITING · via alprazolam · NCT06874452

A Phase 2, Multicenter Open-Label Extension Study to Evaluate the Long-term Safety of Cenobamate in Japanese Subjects With Partial Onset SeizuresPHASE2

RECRUITING · via cenobamate · NCT06590896

Leveraging Biomarkers for Personalized Treatment of Alcohol Use Disorder Comorbid With Post Traumatic Stress DisorderPHASE2

RECRUITING · via topiramate · NCT03667846

Safety, Tolerability and Pharmacokinetics of Single and Multiple Oral Doses of BI 3031185 in Japanese Healthy Male Trial Participants (Single-blind, Randomised, Placebo-controlled, Parallel Group Design) and Effect of Multiple Doses of BI 3031185 on Pharmacokinetics of a Single Dose of a Combination of Drospirenone and Ethinylestradiol (Oral Contraceptive) in Japanese Healthy Female Trial Participants (Non-randomised, Open-label, Fixed Sequence Design)PHASE1

NOT_YET_RECRUITING · via Midazolam · NCT07656792

An Open-label, Single-arm, Fixed-sequence Phase I Clinical Trial to Evaluate the Effect of HRS-1301 Tablets on the Pharmacokinetics of Midazolam and Atorvastatin Calcium Tablets in Healthy ParticipantsPHASE1

RECRUITING · via Midazolam · NCT07608705

AN OPEN-LABEL PHASE 1 STUDY TO EVALUATE PF-07994525 IN PARTICIPANTS WITH ADVANCED MALIGNANCIESPHASE1

RECRUITING · via Midazolam · NCT07426757

A Multi-part, Phase 1, First-Time-in-Human Study to Investigate Safety, Tolerability, and PK of VH4770359 in Healthy ParticipantsPHASE1

NOT_YET_RECRUITING · via Midazolam · NCT07525544

A Phase I, Single-center, Open-Label, Single-Arm, Fixed-Sequence Study to Evaluate the Drug-Drug Interaction of HDM1002 and Metformin, Empagliflozin, Midazolam, Valsartan, and Warfarin in Overweight/Obese Adult Chinese SubjectsPHASE1

RECRUITING · via Midazolam · NCT07331389

A Randomized, Parallel, Open-label With Blinded Assessment Study Comparing Hemodynamic Profiles Between Remimazolam- and Propofol-based Total Intravenous Anesthesia in Patients Undergoing Robot-assisted Gynecologic SurgeryNA

NOT_YET_RECRUITING · via propofol · NCT07251101

Clinical and Molecular Mechanism Study of Remimazolam Regulating the N/OFQ-inflammation-immune Axis to Optimize the Effect of General Anesthesia in Gynecological SurgeryNA

NOT_YET_RECRUITING · via propofol · NCT06990763

Effects of an Opioid Sparing Care Pathway for Patients Undergoing Obesity SurgeryNA

RECRUITING · via propofol · NCT03756961

The Effect of Sevoflurane and Desflurane Anesthetic Agents Used in Elective Cholecystectomy Surgery on Heme Oxygenase-1 mRNA Expression and Heme Oxygenase-1 Protein Levels: A Comparative Prospective StudyPHASE4

WITHDRAWN · via sevoflurane · NCT06457958

A Multicenter Open Study of the Efficacy of Mianserin in Combination With SSRIs in Patients With Depression With Sleep ProblemsPHASE4

UNKNOWN · via lorazepam · NCT05599126

Comparison of the Use of Propofol and Nasal Dexmedetomidine in the Management of Agitation and Delirium in Patients Undergoing Dental ProceduresPHASE4

COMPLETED · via propofol · NCT06466915

Clinical Study on Sedative Effect and Safety of Remimazolam Besylate in ARDS Patients With Mechanical VentilationPHASE4

UNKNOWN · via Midazolam · NCT05758597

Cerebral Hemodynamic and Metabolic Responses to Anesthesia and Vasopressors in Adult Surgery: A 2x2 Factorial Design Randomized Controlled Trial With Light-based Neuromonitoring (CHEM-FACT Study)PHASE4

UNKNOWN · via propofol · NCT05941494

The Efficacy and Safety of First-Line Anti-Epileptic Drugs (AEDs) as Substitution Therapy in Children Who Are Resistant to Second-Line AEDsPHASE4

UNKNOWN · via clobazam · NCT05697614

Zolmitriptane as Prophylactic Therapy Childhood MigrainePHASE4

UNKNOWN · via topiramate · NCT06089356

Hemodynamic Effects of Ketamine Compared With Propofol as Continuous ICU Sedation in Mechanically Ventilated PatientsPHASE4

COMPLETED · via propofol · NCT06243822

The Effect Of Adding Ketamine to Propofol For Drug-induced Sleep Endoscopy in Adult Patients With Obstructive Sleep Apnea A Randomized Controlled StudyPHASE4

UNKNOWN · via propofol · NCT04452383

DExmEdetomidine Sedation Versus Propofol SEDATION FOR Catheter ABLATION of Atrial Fibrillation Under a Cardiologist Supervision: A Randomized Controlled Pilot STUDYPHASE4

COMPLETED · via propofol · NCT03844841

Comparison of Procedural Sedation With Propofol and Dexmedetomidine During Transcatheter Aortic Valve Implantation Using the Transfemoral Approach: Randomized Double Blind Prospective StudyPHASE4

COMPLETED · via propofol · NCT03747432

Delirium Reduction by Volatile Anesthesia in Cardiac Surgery: Prospective, Randomized, Single-blinded StudyPHASE4

COMPLETED · via propofol · NCT03729011

Ketamine Co-induction for Patients With Major Depressive Disorder; a Randomized Clinical TrialPHASE4

UNKNOWN · via propofol · NCT03666494

Determination of Dose-response Curves Between Propofol Concentration and Intraoperative Electroencephalographic Patterns Until Burst SuppressionPHASE4

COMPLETED · via propofol · NCT04345926

Evaluation of Automated Delivery of Propofol Using Closed-Loop Anaesthesia Delivery System in Patients Undergoing Thoracic Surgery: A Randomised Controlled StudyPHASE4

COMPLETED · via propofol · NCT03307551

ClinicalTrials.gov via the drug-target graph.

What's happening now

Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for 7 drugs that target this protein, plus publications where such a drug is a genuine subject. Every item is reached indirectly through the drug, not the protein itself; incidental mentions (a paper that merely measures a drug) and press items are excluded.

Trial status changed2026-08-13
NMDAR Modulation As a Therapeutic Target and Probe of Neural Dysfunction in OCD
Status changed to Completed · ClinicalTrials.gov · via Midazolam
Regulatory approval2026-07-22
Approval: TOPIRAMATE (ANDA220943)
fda · regulatory · fda · via topiramate
Trial status changed2026-07-22
A Phase 1, 3-part, Open-label Study to Evaluate the Effects of KarXT Administration on the Pharmacokinetics of Midazolam, Fexofenadine, and Digoxin in Healthy Adult Participants
Status changed to Completed · ClinicalTrials.gov · via Midazolam
Trial status changed2026-07-20
A Phase 1 Study to Evaluate the Effect of Multiple Doses of ABBV-722 on the Pharmacokinetics of Cocktail Probe Substrates of CYP3A and Select Transporters in Healthy Adult Subjects
Status changed to Active, not recruiting · ClinicalTrials.gov · via Midazolam
Regulatory approval2026-07-14
Approval: PROPOFOL (ANDA220857)
fda · regulatory · fda · via propofol
Regulatory approval2026-07-13
Approval: ALPRAZOLAM (ANDA213204)
fda · regulatory · fda · via alprazolam
Trial status changed2026-07-13
Mechanistic Investigation of Therapies for Down Syndrome Regression Disorder
Status changed to Completed · ClinicalTrials.gov · via lorazepam
Product recall2026-07-06
Recall (Class III): TOPIRAMATE
fda · safety · fda · via topiramate
Supplemental approval2026-06-29
Supplemental approval: PHENTERMINE AND TOPIRAMATE (NDA022580)
fda · regulatory · fda · via topiramate
New publication2025-02-08
Neonatal sevoflurane exposures inhibits DHHC5-mediated palmitoylation of TfR1 in oligodendrocytes, leading to hypomyelination and neurological impairments.
Journal of advanced research · 2025 · 9 citations · Europe PMC · via sevoflurane
Product recall2024-11-18
Recall (Class I): CLONAZEPAM
fda · safety · fda · via clonazepam
Safety communication2024-06-20
Drug Safety Update: Topiramate (Topamax): introduction of new safety measures, including a Pregnancy Prevention Programme
mhra · safety · mhra · via topiramate

Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.